基于网络药理学及分子对接技术分析蠲痹汤加减治疗类风湿关节炎的作用机制  

Molecular Mechanisms of Modified Juanbi Tang(蠲痹汤加减)on Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking

作　　者：亓伟钰 李鑫[1] 满荣勇[2] 曹建中 QI Wei-yu;LI Xin;MAN Rong-yong;CAO Jian-zhong(Hunan Provincial Key Laboratory of Diagnostics of Chinese Medicine,Hunan University of Chinese Medicine,Changsha Hunan 410208,China;The First People's Hospital of Huaihua,Huaihua Hunan 418000,China)

机构地区：[1]湖南中医药大学中医诊断学湖南省重点实验室,湖南长沙410208 [2]怀化市第一人民医院,湖南怀化418000

出　　处：《中医药导报》2022年第4期105-111,共7页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金青年科学基金项目(81803993)。

摘　　要：目的:运用网络药理学及分子对接等策略,对蠲痹汤加减治疗类风湿关节炎(RA)的生物学机制进行探索。方法:运用TCMSP数据库筛选蠲痹汤加减所含药物中符合口服生物利用度≥30%和类药性≥0.18的化合物及其作用靶点。通过GeneCards、OMIM、TTD和Drugbank数据库查找RA相关基因靶点,利用韦恩图得到药物与疾病交集靶点,采用Cytoscape3.7.1软件构建化合物-靶点网络,利用STRING数据库进行蛋白互作分析。运用GO和KEGG数据库对关键靶点进行功能注释和信号通路富集分析。利用Autodock、PyMol等软件对核心化合物及靶点进行分子对接与可视化,探讨蠲痹汤治疗RA的可能作用机制。结果:172个化学成分、223个成分靶标和2933个疾病靶标与RA关系密切。蠲痹汤与RA共有靶点157个,GO富集显示这些靶点功能主要有氧化应激应答、脂多糖应答、细菌来源分子应答和RNA聚合酶Ⅱ特异性DNA结合转录因子等。KEGG富集的通路主要有PI3K/AKT、AGE/RAGE、TNF、IL-17、雌激素受体及Th17细胞分化等,这些通路主要参与抗炎和免疫调控。分子对接结果显示,槲皮素、柚皮素、山奈酚结构与JUN、MAPK3、TP53靶点蛋白结合较好,存在多种相互作用。结论:基于当前证据,蠲痹汤加减治疗类风湿关节炎主要是通过调控自身免疫、氧化应激、炎症反应、脂质代谢等途径,作用于免疫调节、抗炎等多环节,以达到治疗目的。Objective:To predict the molecular mechanisms of Modified Juanbi Tang in the treatment of rheumatoid arthritis(RA)by network pharmacology and molecular docking.Methods:The active ingredients and corresponding molecular targets of Juanbi Tang were retrieved from TCMSP database,with bioavailability≥30%and drug resistance≥0.18.The molecular targets of RA disease were obtained from searching GeneCards,OMIM,TTD and Drugbank.The common targets between Juanbi Tang and RA were obtained through Venn mapping.The drug-target interactions were mapped with Cytoscape3.7.1 and protein-protein interactions were mapped with STRING.GO and KEGG were used to enrich the molecule functions and pathways of the target genes.Autodock and PyMol were used for molecular docking and visualization of binding of core compounds and corresponding targets,to explore the possible mechanism of Juanbi Tang in the treatment of RA.Results:A total of 172 chemical components,223 ingredients and 2933 gene targets were identified in the database and157 of the genes were common for both Juanbi Tangible and RA.GO enrichment showed that the main functions of these targets were oxidative stress response,lipopolysaccharide response,bacterial derived molecular response and RNA polymerase Ⅱ specific DNA binding transcription factor.KEGG analysis revealed that PI3K/AKT,AGE/RAGE,TNF,IL-17,estrogen receptor and Th17 cell differentiation pathways were the major pathways involving the treatment of RA by Juanbi Tang.And these pathways are mainly involved in anti-inflammatory and immune regulation.According to molecular docking results,quercetin,naringin and kaempferol showed a good interaction with the target proteins JUN,MAPK3 and TP53.Conclusion:The possible molecular mechanisms of Modified Juanbi Tang on RA,mainly include the regulation of autoimmunity,oxidative stress,inflammatory response,lipid metabolism and other ways,acting on immune regulation,anti-inflammatory and other links,so as to achieve the purpose of treatment.

关 键 词：类风湿关节炎 蠲痹汤加减 网络药理学 分子对接 炎症 

分 类 号：R259.932.2[医药卫生—中西医结合]